@article{TshitengeTshitengeBruhnFeineisetal.2019, author = {Tshitenge Tshitenge, Dieudonn{\´e} and Bruhn, Torsten and Feineis, Doris and Mudogo, Virima and Kaiser, Marcel and Brun, Reto and Bringmann, Gerhard}, title = {An unusually broad series of seven cyclombandakamines, bridged dimeric naphthylisoquinoline alkaloids from the Congolese liana Ancistrocladus ealaensis}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-46336-z.}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200759}, pages = {9812}, year = {2019}, abstract = {A series of seven unusual dimeric naphthylisoquinoline alkaloids was isolated from the leaves of the tropical liana Ancistrocladus ealaensis J. L{\´e}onard, named cyclombandakamine A (1), 1-epi-cyclombandakamine A (2), and cyclombandakamines A3-7 (3-7). These alkaloids have a chemically thrilling structural array consisting of a twisted dihydrofuran-cyclohexenone-isochromene system. The 1′″-epimer of 4, cyclombandakamine A1 (8), had previously been discovered in an unidentified Ancistrocladus species related to A. ealaensis. Both lianas produce the potential parent precursor, mbandakamine A (9), but only A. ealaensis synthesizes the corresponding cyclized form, along with a broad series of slightly modified analogs. The challenging isolation required, besides multi-dimensional chromatography, the use of a pentafluorophenyl stationary phase. Featuring up to six stereocenters and two types of chiral axes, their structures were elucidated by means of 1D and 2D NMR, HRESIMS, in combination with oxidative chemical degradation experiments as well as chiroptical (electronic circular dichroism spectroscopy) and quantum chemical calculations. Compared to the 'open-chain' parent compound 9, these dimers displayed rather moderate antiplasmodial activities.}, language = {en} } @article{FayezFeineisAkeAssietal.2019, author = {Fayez, Shaimaa and Feineis, Doris and Ak{\´e} Assi, Laurent and Seo, Ean-Jeong and Efferth, Thomas and Bringmann, Gerhard}, title = {Ancistrobreveines A-D and related dehydrogenated naphthylisoquinoline alkaloids with antiproliferative activities against leukemia cells, from the West African liana Ancistrocladus abbreviatus}, series = {RSC Advances}, volume = {9}, journal = {RSC Advances}, number = {28}, doi = {10.1039/C9RA03105G}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201686}, pages = {15738-15748}, year = {2019}, abstract = {A unique series of six biaryl natural products displaying four different coupling types (5,10 , 7,10 , 7,80 , and 5,80) were isolated from the roots of the West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Although at first sight structurally diverse, these secondary metabolites all have in common that they belong to the rare group of naphthylisoquinoline alkaloids with a fully dehydrogenated isoquinoline portion. Among the African Ancistrocladus species, A. abbreviatus is so far only the second one that was found to produce compounds with such a molecular entity. Here, we report on four new representatives, named ancistrobreveines A-D (12-14, and 6). They were identified along with the two known alkaloids 6-O-methylhamateine (4) and entdioncophylleine A (10). The two latter naphthylisoquinolines had so far only been detected in Ancistrocladus species from Southeast Asia. All of these fully dehydrogenated alkaloids have in common being optically active despite the absence of stereogenic centers, due to the presence of the rotationally hindered biaryl axis as the only element of chirality. Except for ent-dioncophylleine A (10), which lacks an oxygen function at C-6, the ancistrobreveines A-D (12-14, and 6) and 6-O-methylhamateine (4) are 6-oxygenated alkaloids, and are, thus, typical 'Ancistrocladaceae-type' compounds. Ancistrobreveine C (14), is the first - and so far only - example of a 7,80-linked fully dehydrogenated naphthylisoquinoline discovered in nature that is configurationally stable at the biaryl axis. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR) and chiroptical (electronic circular dichroism) methods. Ancistrobreveine C (14) and 6-O-methylhamateine (4) exhibited strong antiproliferative activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrugresistant subline, CEM/ADR5000.}, language = {en} } @article{BruennertSeupelGoyaletal.2023, author = {Br{\"u}nnert, Daniela and Seupel, Raina and Goyal, Pankaj and Bach, Matthias and Schraud, Heike and Kirner, Stefanie and K{\"o}ster, Eva and Feineis, Doris and Bargou, Ralf C. and Schlosser, Andreas and Bringmann, Gerhard and Chatterjee, Manik}, title = {Ancistrocladinium A induces apoptosis in proteasome inhibitor-resistant multiple myeloma cells: a promising therapeutic agent candidate}, series = {Pharmaceuticals}, volume = {16}, journal = {Pharmaceuticals}, number = {8}, issn = {1424-8247}, doi = {10.3390/ph16081181}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362887}, year = {2023}, abstract = {The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.}, language = {en} } @article{FayezFeineisMudogoetal.2017, author = {Fayez, Shaimaa and Feineis, Doris and Mudogo, Virima and Awale, Suresh and Bringmann, Gerhard}, title = {Ancistrolikokines E-H and related 5,8\('\)-coupled naphthylisoquinoline alkaloids from the Congolese liana \(Ancistrocladus\) \(likoko\) with antiausterity activities against PANC-1 human pancreatic cancer cells}, series = {RSC Advances}, volume = {7}, journal = {RSC Advances}, number = {85}, doi = {10.1039/c7ra11200a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172008}, pages = {53740-53751}, year = {2017}, abstract = {A striking feature of the metabolite profile of \(Ancistrocladus\) \(likoko\) (Ancistrocladaceae) is the exclusive production of 5,8\('\)-linked naphthylisoquinoline alkaloids varying in their OMe/OH substitution patterns and in the hydrogenation degree in their isoquinoline portions. Here we present nine new compounds of this coupling type isolated from the twigs of this remarkable Central African liana. Three of them, the ancistrolikokines E (9), E\(_2\) (10), and F (11), are the first 5,8\('\)-linked naphthyldihydroisoquinolines found in nature with \(R\)-configuration at C-3. The fourth new metabolite, ancistrolikokine G (12), is so far the only representative of the 5,8\('\)-coupling type that belongs to the very rare group of alkaloids with a fully dehydrogenated isoquinoline portion. Moreover, five new \(N\)-methylated naphthyltetrahydroisoquinolines, named ancistrolikokines A\(_2\) (13), A\(_3\) (14), C\(_2\) (5), H (15), and H\(_2\) (16) are presented, along with six known 5,8\('\)-linked alkaloids, previously identified in related African \(Ancistrocladus\) species, now found for the first time in \(A.\) \(likoko\). The structural elucidation was achieved by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and by chemical (oxidative degradation) and chiroptical (electronic circular dichroism) methods. The new ancistrolikokines showed moderate to good preferential cytotoxic activities towards pancreatic PANC-1 cells in nutrient-deprived medium (NDM), without causing toxicity under normal, nutrient-rich conditions, with ancistrolikokine H\(_2\) (16) being the most potent compound.}, language = {en} } @article{TshitengeFeineisMudogoetal.2017, author = {Tshitenge, Dieudonn{\´e} Tshitenge and Feineis, Doris and Mudogo, Virima and Kaiser, Marcel and Brun, Reto and Bringmann, Gerhard}, title = {Antiplasmodial Ealapasamines A-C,'Mixed' Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {5767}, doi = {10.1038/s41598-017-05719-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170645}, year = {2017}, abstract = {Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1-3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. L{\´e}onard. These 'mixed', constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1-3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range.}, language = {en} } @article{MufusamaFeineisMudogoetal.2019, author = {Mufusama, Jean-Pierre and Feineis, Doris and Mudogo, Virima and Kaiser, Marcel and Brun, Reto and Bringmann, Gerhard}, title = {Antiprotozoal dimeric naphthylisoquinolines, mbandakamines B\(_3\) and B\(_4\), and related 5,8′-coupled monomeric alkaloids, ikelacongolines A-D, from a Congolese Ancistrocladus liana}, series = {RSC Advances}, volume = {9}, journal = {RSC Advances}, number = {21}, doi = {10.1039/C9RA01784D}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201141}, pages = {12034-12046}, year = {2019}, abstract = {From the leaves of a botanically and phytochemically as yet unexplored Ancistrocladus liana discovered in the rainforests of the Central region of the Democratic Republic of the Congo in the vicinity of the town of Ikela, six new naphthylisoquinoline alkaloids were isolated, viz., two constitutionally unsymmetric dimers, the mbandakamines B\(_3\) (3) and B\(_4\) (4), and four related 5,8′-linked monomeric alkaloids, named ikelacongolines A-D (5a, 5b, 6, and 7). The dimers 3 and 4 are structurally unusual quateraryls comprising two 5,8′-coupled monomers linked via a sterically strongly constrained 6′,1′′-connection between their naphthalene units. These compounds contain seven elements of chirality, four stereogenic centers and three consecutive chiral axes. They were identified along with two known related compounds, the mbandakamines A (1) and B\(_2\) (2), which had so far only been detected in two Ancistrocladus species indigenous to the Northwestern Congo Basin. In addition, five known monomeric alkaloids, previously found in related Central African Ancistrocladus species, were isolated from the here investigated Congolese liana, three of them belonging to the subclass of 5,8′-coupled naphthylisoquinoline alkaloids, whereas two compounds exhibited a less frequently occurring 7,8′-biaryl linkage. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR), chemical (oxidative degradation), and chiroptical (electronic circular dichroism) methods. The mbandakamines B\(_3\) (3) and B\(_4\) (4) displayed pronounced activities in vitro against the malaria parasite Plasmodium falciparum and the pathogen of African sleeping sickness, Trypanosoma brucei rhodesiense.}, language = {en} } @article{ZahranAlbohyKhaliletal.2020, author = {Zahran, Eman Maher and Albohy, Amgad and Khalil, Amira and Ibrahim, Alyaa Hatem and Ahmed, Heba Ali and El-Hossary, Ebaa M. and Bringmann, Gerhard and Abdelmohsen, Usama Ramadan}, title = {Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {12}, issn = {1660-3397}, doi = {10.3390/md18120645}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220041}, year = {2020}, abstract = {Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.}, language = {en} } @article{BrixnerKochKullmannetal.2013, author = {Brixner, Tobias and Koch, Federico and Kullmann, Martin and Selig, Ulrike and Nuernberger, Patrick and G{\"o}tz, Daniel C. G. and Bringmann, Gerhard}, title = {Coherent two-dimensional electronic spectroscopy in the Soret band of a chiral porphyrin dimer}, series = {New Journal of Physics}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/15/2/025006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96139}, year = {2013}, abstract = {Using coherent two-dimensional (2D) electronic spectroscopy in fully noncollinear geometry, we observe the excitonic coupling of β,β'-linked bis[tetraphenylporphyrinato-zinc(II)] on an ultrafast timescale in the excited state. The results for two states in the Soret band originating from an excitonic splitting are explained by population transfer with approximately 100 fs from the energetically higher to the lower excitonic state. This interpretation is consistent with exemplary calculations of 2D spectra for a model four-level system with coupling.}, language = {en} } @article{WangLiKateleetal.2014, author = {Wang, Hui and Li, Min-Yi and Katele, F{\´e}lix Zongwe and Satyanandamurty, Tirumani and Wu, Jun and Bringmann, Gerhard}, title = {Decandrinin, an unprecedented \(C_9\)-spiro-fused 7,8-\( seco-ent\)-abietane from the Godavari mangrove \(Ceriops\ decandra\)}, series = {Beilstein Journal of Organic Chemistry}, volume = {10}, journal = {Beilstein Journal of Organic Chemistry}, issn = {1860-5397}, doi = {10.3762/bjoc.10.23}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119983}, pages = {276-81}, year = {2014}, abstract = {Decandrinin (1), an unprecedented \(C_9\)-spiro-fused 7,8-\(seco-ent\)-abietane, was obtained from the bark of an Indian mangrove, \(Ceriops\ decandra\), collected in the estuary of Godavari, Andhra Pradesh. The constitution and the relative configuration of 1 were determined by HRMS (ESI) and extensive NMR investigations, and the absolute configuration by circular dichroism (CD) and optical-rotatory dispersion (ORD) spectroscopy in combination with quantum-chemical calculations. Decandrinin is the first 7,8-\(seco-ent\)-abietane.}, language = {en} } @article{JansenOhlendorfErhardetal.2013, author = {Jansen, Nils and Ohlendorf, Birgit and Erhard, Arlette and Bruhn, Torsten and Bringmann, Gerhard and Imhoff, Johannes F.}, title = {Helicusin E, Isochromophilone X and Isochromophilone XI: New Chloroazaphilones Produced by the Fungus Bartalinia robillardoides Strain LF550}, series = {Marine Drugs}, volume = {11}, journal = {Marine Drugs}, number = {3}, doi = {10.3390/md11030800}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129649}, pages = {800-816}, year = {2013}, abstract = {Microbial studies of the Mediterranean sponge Tethya aurantium led to the isolation of the fungus Bartalinia robillardoides strain LF550. The strain produced a number of secondary metabolites belonging to the chloroazaphilones. This is the first report on the isolation of chloroazaphilones of a fungal strain belonging to the genus Bartalinia. Besides some known compounds (helicusin A (1) and deacetylsclerotiorin (2)), three new chloroazaphilones (helicusin E (3); isochromophilone X (4) and isochromophilone XI (5)) and one new pentaketide (bartanolide (6)) were isolated. The structure elucidations were based on spectroscopic analyses. All isolated compounds revealed different biological activity spectra against a test panel of four bacteria: three fungi; two tumor cell lines and two enzymes.}, language = {en} }